6  Differential Expression Analysis I

Published

October 26, 2025

6.1 Joint analysis of all samples

For the global differential expression analysis, samples from Batches 1 and 2 were analyzed jointly, as both were processed under comparable experimental and sequencing conditions.

The overall distribution of median gene expression values showed that most genes were expressed at low levels across samples, with a steep drop in frequency toward higher expression values. Only a small subset of genes displayed high expression (log₁₀ > 4), consistent with the typical right-skewed distribution of RNA-seq count data. This confirmed that lowly expressed and noise-dominated genes dominated the raw dataset prior to filtering and normalization.

Genes with very low read counts were excluded to minimize technical noise. After filtering for a minimum of 20 counts in at least five samples, approximately 19011 genes were retained for downstream analysis.

  • Filtering removes genes with little information (low counts / expressed in few samples), which stabilizes dispersion estimates and multiple‑testing behavior.

  • The choice of cutoff (20 counts, ≥5 samples) is arbitrary

6.1.1 Liver

6.1.1.1 All mice (male and females)

There are 346 significantly differentially expressed genes (FDR < 0.01, |log2FC| > 1) in the liver between Cre-AAV and GFP control switch mice.

Diagnostic plots for the DE analysis

  • A histogram enriched for low p-values shows the presence of true differential expression (deviation from the uniform null), rather than an all-noise result.
  • The log(baseMean) distribution for significant genes being skewed toward moderate–high counts indicates findings are driven by well-expressed features, not low-count noise that can inflate fold-changes and p-values.
Significantly differentially expressed genes in liver
Cre-AAV and GFP control
(FDR < 0.01, |log2FC| > 1)
gene baseMean log2FoldChange padj
Gstm2-ps1 52.13 -3.85 0.00
Vcp-rs 62.44 -3.22 0.00
Rpl35a-ps2 28.38 -23.87 0.00
Gm10073 32.44 -3.86 0.00
Gm10263 16.80 -5.51 0.00
Gm45855 30.89 -2.76 0.00
Rpl18-ps2 28.35 -3.97 0.00
Gm4332 34.81 -3.75 0.00
Gm8730 49.37 -3.49 0.00
Gm11478 47.92 -3.35 0.00
Gm6548 80.08 -1.26 0.00
ENSMUSG00000143433 27.62 -3.89 0.00
Gm8566 103.10 -3.30 0.00
ENSMUSG00000121793 103.54 -2.85 0.00
Gm4366 55.30 -2.36 0.00
Rpl28-ps1 55.38 -3.03 0.00
ENSMUSG00000135866 244.14 -3.77 0.00
Gm13436 30.54 -3.84 0.00
Eef2-ps2 24.97 -3.75 0.00
Glns-ps1 27.95 -3.44 0.00
Ntn3 95.27 -1.12 0.00
Gm16437 14.49 -3.72 0.00
Gm14586 41.69 -3.27 0.00
Gm15163 37.44 -2.75 0.00
Gm10221 36.85 -3.01 0.00
Lrp1 8347.24 -1.05 0.00
Glo1-ps 42.32 -2.76 0.00
Rps16-ps2 76.01 -2.79 0.00
mt-Ts1 8.25 -6.64 0.00
Gm9816 16.07 -3.07 0.00
Gm10076 1650.81 1.18 0.00
Got2-ps1 56.74 -1.80 0.00
Gm6204 31.50 -3.78 0.00
Gm10232 15.00 -3.22 0.00
Ccdc148 70.68 1.20 0.00
Ftl1-ps1 496.94 -2.43 0.00
Gm5540 31.75 -3.03 0.00
Cox5b-ps 35.84 -2.60 0.00
Gm13611 12.34 -5.37 0.00
Gm5805 13.37 -4.11 0.00
Gm28437 94444.19 1.10 0.00
Gm4149 33.43 -3.11 0.00
Gm9794 71.29 -2.36 0.00
Rpl17-ps3 54.82 -2.66 0.00
Gm12174 25.91 -2.88 0.00
Gm9625 27.50 -2.69 0.00
Gm12350 32.72 -2.86 0.00
Gm8355 42.47 -2.18 0.00
Gm9755 20.01 -3.02 0.00
Rps18-ps5 43.48 -3.87 0.00
Rps26-ps1 18.09 -7.78 0.00
Gm7536 114.42 -2.11 0.00
Rps3a2 74.27 -2.29 0.00
Rps19-ps6 40.54 -2.87 0.00
Hspe1-rs1 36.98 -2.60 0.00
Rpl19-ps11 106.16 -2.18 0.00
ENSMUSG00000128633 88.57 -3.28 0.00
Rps23-ps1 53.86 -2.32 0.00
Gm2962 11.36 -3.15 0.00
Gm12481 52.24 -6.63 0.00
Rpsa-ps10 82.60 -2.28 0.00
Rpl34-ps1 51.23 -4.30 0.00
Llph-ps2 179.22 1.13 0.00
Gm7049 17.26 -3.02 0.00
Gm5835 25.57 -2.69 0.00
Oaz1-ps 127.45 -2.23 0.00
Uba52rt 196.86 -1.83 0.00
Gm5422 13.06 -3.51 0.00
Gm6652 265.61 -1.49 0.00
Rpl7-ps7 12.28 -2.63 0.00
Sap18b 36.69 -2.14 0.00
Akap17a 203.34 -1.21 0.00
Gm12918 83.49 -2.36 0.00
Gm10288 109.88 -2.66 0.00
Rpl35rt 116.67 -2.74 0.00
Eno1b 36.85 -3.70 0.00
Rpl23a-ps3 32.26 -2.57 0.00
Gm7600 15.99 -3.59 0.00
Gm10874 21.01 -2.43 0.00
ENSMUSG00000126438 14.28 -3.17 0.00
Glud-ps 36.25 -2.37 0.00
ENSMUSG00000139771 162.30 -2.77 0.00
mt-Nd6 26837.91 1.17 0.00
Gm11964 10.20 -3.94 0.00
Adrm1b 35.04 -2.70 0.00
Tpt1-ps3 139.00 -2.08 0.00
Gm10039 19.90 -2.65 0.00
Gm5456 15.55 -3.66 0.00
Mif-ps4 9.04 -4.81 0.00
Eif4a-ps4 98.87 -1.64 0.00
Gm4459 14.26 -3.34 0.00
Gm10250 43.21 -2.52 0.00
Gm12183 24.33 -2.54 0.00
Gm12251 15.42 -2.70 0.00
Gm21399 55.48 -2.09 0.00
ENSMUSG00000132147 63.59 -2.52 0.00
ENSMUSG00000137224 123.65 -1.65 0.00
Gm6863 63.19 -1.88 0.00
Rpl6l 21.24 -2.03 0.00
Rps15-ps2 7.66 -3.79 0.00
Gm15772 25.60 -2.69 0.00
Gm6733 14.92 -2.76 0.00
Ap2m1-ps 53.09 -1.93 0.00
Rps10-ps1 15.37 -3.88 0.00
Abca2 551.64 -1.28 0.00
Gm10163 31.62 -2.42 0.00
Pgam1-ps2 23.48 -2.62 0.00
Gm9616 13.98 -2.96 0.00
Gm15427 76.23 -2.77 0.00
Hspd1-ps3 55.65 -1.85 0.00
Gm7658 12.59 -2.57 0.00
Gm10053 99.63 -2.26 0.00
ENSMUSG00000131289 19.95 -2.81 0.00
Gm5560 20.73 -2.38 0.00
Gpi-ps 16.57 -2.79 0.00
Gm5452 24.48 -2.73 0.00
Gm6180 6.74 -3.44 0.00
Gm6170 11.84 -2.94 0.00
Rps25-ps1 15.45 -3.02 0.00
Gm9385 49.90 -2.63 0.00
Rps27a-ps2 53.04 -1.80 0.00
Gm7666 39.32 -2.39 0.00
Abca3 1133.90 -1.00 0.00
Gm37035 190.24 -1.00 0.00
Rpl14-ps1 52.91 -1.94 0.00
mt-Nd5 125169.00 1.02 0.00
Rps18-ps6 75.96 -2.62 0.00
ENSMUSG00000132604 23.58 -3.13 0.00
Gm28661 135299.60 1.02 0.00
Pam16l 10.60 -2.62 0.00
Ndufb4c 283.83 1.04 0.00
Gm16439 37.11 -2.33 0.00
Gm12346 20.50 -2.19 0.00
Ptprf 2352.48 -1.07 0.00
Gm44170 66.86 -2.04 0.00
Rab11b-ps2 4.76 -4.18 0.00
Gm9892 20.33 -1.89 0.00
Gm7816 22.48 -2.25 0.00
Gm13461 11.64 -2.72 0.00
Gm7336 369.13 -1.11 0.00
Gm6055 9.53 -2.34 0.00
Gm7730 10.33 -3.42 0.00
Rpl31-ps8 41.91 -1.80 0.00
Fn1 19461.02 -1.02 0.00
Gm9826 135.93 -2.26 0.00
Gm5424 947.45 -1.97 0.00
ENSMUSG00000126686 64.44 1.11 0.00
Gm13456 473.36 -1.91 0.00
Tpm3-rs7 18.97 -1.95 0.00
ENSMUSG00000130204 43.03 -1.68 0.00
Gm6789 99.15 -1.63 0.00
Gm7204 18.21 -2.05 0.00
Gm13680 15.05 -2.66 0.00
Hadhb-ps 140.94 -1.56 0.00
ENSMUSG00000132256 10.60 -2.77 0.00
Gm2225 9.96 -2.66 0.00
Eif3j2 60.64 -1.70 0.00
Gm9493 34.64 -2.14 0.00
ENSMUSG00000125136 7.80 -2.42 0.00
Atp6v0c-ps2 7.96 -2.29 0.00
ENSMUSG00000123407 9.32 -3.27 0.00
Nphs1 4.88 3.13 0.00
Rpl17-ps10 73.91 -1.90 0.00
Gm5499 5.05 -3.18 0.00
Gm6136 60.21 -1.64 0.00
ENSMUSG00000122915 12.16 -3.41 0.00
Tmppe 31.49 -1.00 0.00
Kpna2rt 15.98 -2.27 0.00
Gm10819 6.88 -3.14 0.00
Rps6-ps4 144.91 -1.48 0.00
Gm5182 10.02 -2.79 0.00
Actr3-ps 10.09 -2.27 0.00
Gm57504 13.10 -1.79 0.00
Mmp15 522.08 -1.23 0.00
AK157302 6.50 -3.00 0.00
Rpl9-ps4 20.50 -2.22 0.00
Mrpl23-ps1 12.34 -2.36 0.00
Gm8203 6.24 -3.24 0.00
Wdr89 87.06 -1.08 0.00
Gm4202 7.20 -2.76 0.00
Tmed2b 22.20 -1.74 0.00
Tpi-rs11 5.25 -3.69 0.00
ENSMUSG00000140707 19.38 1.19 0.00
ENSMUSG00000125175 21.20 -2.01 0.00
Kcp 52.56 -1.44 0.00
ENSMUSG00000133704 22.57 -1.87 0.00
Mov10 216.85 -1.05 0.00
Gm20056 12.66 -2.19 0.00
Gm6206 14.32 -1.86 0.00
Rps24-ps3 28.02 -2.24 0.00
Gm10036 13.35 -2.39 0.00
Rps10-ps2 49.17 -1.55 0.00
ENSMUSG00000121784 135.87 -1.36 0.00
Gm12992 72.44 -1.18 0.00
ENSMUSG00000128869 8.51 -3.93 0.00
Btf3-ps1 20.61 -1.83 0.00
Rps15a-ps7 16.53 -2.49 0.00
Gm45507 179.36 1.18 0.00
Gm12254 24.06 -1.73 0.00
Rps13-ps1 33.55 -2.34 0.00
Gm6344 12.70 -2.75 0.00
Gm44442 273.09 -1.27 0.00
Rpl36a-ps2 19.83 -2.03 0.00
Rps2-ps10 25.90 -8.30 0.00
Col1a1 50.99 -1.14 0.00
Gm5436 11.73 -2.70 0.00
Gm12966 13.65 -1.95 0.00
Rplp2-ps1 25.89 -3.58 0.00
Gm14494 11.73 -2.17 0.00
Gm15542 55.44 -1.04 0.00
Impdh2-ps 10.80 -2.00 0.00
Gm10252 12357.65 1.20 0.00
Psma5-ps 19.33 -2.05 0.00
Mir6236 26.56 -1.80 0.00
Gm5421 8.23 -2.68 0.00
Gm2223 17.68 -1.81 0.00
ENSMUSG00000121777 558.33 -1.39 0.00
Nudc-ps1 6.65 -3.03 0.00
Gm2614 8.27 -2.86 0.00
Hspb1 382.47 -1.06 0.00
Gm22009 33.05 2.72 0.00
Rn7s1 890.15 1.74 0.00
Rpl36-ps12 39.43 -1.71 0.00
Gm13835 78.41 -1.28 0.00
Ahcyl 1153.38 -1.36 0.00
Ube2srt 6.21 -2.80 0.00
ENSMUSG00000121655 23.67 -1.91 0.00
Gm5905 24.65 -2.00 0.00
Gstp-ps 125.10 -3.28 0.00
Kansl2-ps 4.89 -2.21 0.00
Nrtn 24.00 -1.39 0.00
Rpl3-ps1 95.37 -1.26 0.00
Rpl15-ps3 44.55 -3.99 0.00
Hcn3 87.03 -1.69 0.00
Bhmt1b 952.66 -1.92 0.00
Dmbt1 53.46 4.28 0.00
Gm5884 13.14 -1.24 0.00
Gm4633 12.02 1.15 0.00
Fam222a 32.22 -1.76 0.00
Zbtb42 82.80 -1.04 0.00
ENSMUSG00000130316 15.04 -1.26 0.00
Pcbp3 15.89 -1.15 0.00
ENSMUSG00000123794 29.55 -1.12 0.00
Gm15519 10.05 -2.68 0.00
Cd28 8.33 1.42 0.00
Atp11a 291.46 -1.06 0.00
Mxd4os1 27.79 -1.01 0.00
Rpsa-ps2 9.06 -2.71 0.00
ENSMUSG00000123149 23.72 -1.60 0.00
Csnk2a1-ps3 22.75 -1.44 0.00
Gm8399 6.88 -2.74 0.00
Gm57397 11.52 1.24 0.00
Rps27rt 157.04 -1.88 0.00
Slc41a2 285.10 -1.73 0.00
Gm19918 8.67 -2.16 0.00
Gm9531 7.57 -2.05 0.00
Rps18-ps3 16.40 -3.70 0.00
ENSMUSG00000121644 23.40 -1.17 0.00
Gm57204 33.56 1.17 0.00
ENSMUSG00000121608 17.33 -1.51 0.00
Mrip-ps 5.74 -2.33 0.00
Col15a1 67.78 -1.06 0.00
ENSMUSG00000124469 21.16 1.10 0.00
P2ry10 12.74 1.37 0.00
ENSMUSG00000128964 19.69 1.07 0.00
Fasn 2164.04 -1.70 0.00
Apold1 61.53 1.02 0.00
Gadl1 7.53 -2.14 0.00
Gm20707 8.35 1.45 0.00
Rpl10a-ps1 95.72 -1.04 0.00
Gm2999 8.24 -2.33 0.00
Gm28439 601.79 2.04 0.00
Gm3571 12.88 -3.44 0.00
Atp5pb-ps 30.83 -1.38 0.00
Scp2-ps2 144.46 -3.35 0.00
4921516A02Rik 55.19 -1.29 0.00
ENSMUSG00000141850 8.45 -2.83 0.00
Fosb 22.06 2.04 0.00
Rn7sk 199.48 1.54 0.00
Gm11266 38.55 1.06 0.00
ENSMUSG00000130839 10.88 1.18 0.00
Cd83 83.20 1.13 0.00
ENSMUSG00000121483 27.23 1.15 0.00
Rps13-ps2 21.74 -2.87 0.00
Gm12191 12.12 -4.12 0.00
Lpar2 21.24 -1.43 0.00
Rpl9-ps6 185.94 -1.45 0.00
Tcea1-ps1 12.53 -1.26 0.00
Ndufb4b 108.41 1.77 0.00
Btf3l4b 25.24 -1.55 0.00
Gm10052 12.79 -1.58 0.00
Gm49518 11.75 1.44 0.00
Gm15890 37.52 1.01 0.00
Gm12669 24.92 -1.14 0.00
Isyna1 86.77 -1.14 0.00
mt-Atp8 9801.93 1.55 0.00
Gm3724 5.21 -1.65 0.00
Ube2n-ps1 5.08 -2.61 0.00
ENSMUSG00000122459 31.76 1.25 0.00
Rpl37rt 21.92 -4.22 0.00
Bhmt-ps1 48.28 -1.35 0.00
Rps7-ps3 54.83 -2.72 0.00
Cd276 39.82 -1.44 0.00
P2ry10b 19.13 1.10 0.00
Gm16098 27.84 1.26 0.00
Cldn7 9.09 1.19 0.00
Gm10157 25.10 -1.20 0.00
ENSMUSG00000141552 13.85 1.10 0.00
Spdya 14.28 1.12 0.00
Nutf2-ps1 18.49 -1.32 0.00
Gm6477 9.58 -1.59 0.00
ENSMUSG00000138427 84.83 -2.84 0.00
Arg2 11.81 1.28 0.00
Gm29216 7900.22 -2.54 0.00
Gm5526 11.40 -3.82 0.00
Ms4a6b 58.12 1.01 0.00
Dpy19l3 159.02 -2.12 0.00
ENSMUSG00000134769 28.13 1.45 0.00
Ihh 30.63 -2.25 0.01
Saa1 1967.87 -2.16 0.01
Gm57587 9.64 1.09 0.01
Gm21974 11.66 -1.92 0.01
Mmp7 13.34 1.82 0.01
Gm10222 6611.33 1.79 0.01
Gm49190 37.10 -1.14 0.01
Gm33543 308.55 1.07 0.01
Idi1-ps2 29.11 1.09 0.01
Zfp1008 9.59 1.22 0.01
Gm9824 12.36 -1.37 0.01
ENSMUSG00000129906 37.01 -2.48 0.01
Rab7-ps1 9.67 -1.35 0.01
Gm4735 44.77 -3.99 0.01
Gm10095 16.23 -1.20 0.01
Klrb1c 18.98 1.00 0.01
Gm14121 3.52 -1.87 0.01
ENSMUSG00000127021 4.50 1.38 0.01
Gm9761 14.38 -1.16 0.01
Hmgb1-ps3 5.58 2.55 0.01
Hcn2 7.64 -1.52 0.01
Gm28706 19.94 1.05 0.01
Ifitm6 11.85 1.20 0.01
Gm12522 16.44 -2.71 0.01
Gm56696 5.78 1.40 0.01
Ankrd9 31.04 -1.04 0.01
Gm47544 46.69 -1.35 0.01
ENSMUSG00000140389 6.64 1.06 0.01

6.1.1.2 Males only

There are 279 significantly differentially expressed genes (FDR < 0.01, |log2FC| > 1) in the liver between Cre-AAV and GFP control switch mice.

Diagnostic plots for the DE analysis

  • A histogram enriched for low p-values shows the presence of true differential expression (deviation from the uniform null), rather than an all-noise result.
  • The log(baseMean) distribution for significant genes being skewed toward moderate–high counts indicates findings are driven by well-expressed features, not low-count noise that can inflate fold-changes and p-values.
Significantly differentially expressed genes in liver
Cre-AAV and GFP control
(FDR < 0.01, |log2FC| > 1)
gene baseMean log2FoldChange padj
Rn7s1 830.76 2.39 0.00
Gm12481 45.12 -8.87 0.00
Gm22009 29.41 3.65 0.00
Gm10076 1286.01 1.35 0.00
Rpl35a-ps6 41.21 -21.68 0.00
Rpl35a 3531.67 1.04 0.00
Ulk1 1029.37 -1.06 0.00
Dll1 39.41 -1.37 0.00
Gm15387 14.61 -7.24 0.00
mt-Nd6 24270.23 1.30 0.00
Vcp-rs 55.47 -2.88 0.00
Sipa1l3 84.90 -1.16 0.00
Gm8566 77.66 -3.20 0.00
Abca2 568.48 -1.54 0.00
Apoc2l 454.65 1.04 0.00
Rpl18-ps2 21.59 -4.65 0.00
Ndufb1 899.87 1.07 0.00
Fgfr4 482.85 -1.00 0.00
Lrp1 8088.56 -1.17 0.00
Gstm2-ps1 48.05 -3.53 0.00
Tenm3 311.48 -1.01 0.00
Ptprf 2390.07 -1.20 0.00
Gm45855 26.12 -2.74 0.00
Slco2a1 801.63 -1.18 0.00
Mov10 223.14 -1.31 0.00
Gm10263 12.62 -5.89 0.00
Gm10073 25.25 -3.56 0.00
Rn7sk 180.23 2.01 0.00
ENSMUSG00000143433 24.43 -4.19 0.00
Kcp 60.71 -1.75 0.00
Slc26a1 2306.99 -1.12 0.00
Gm28437 84421.94 1.22 0.00
Gm4332 26.92 -3.57 0.00
Eef2-ps2 21.89 -3.87 0.00
Ttyh3 146.91 -1.02 0.00
Tmppe 29.09 -1.47 0.00
Rpl28-ps1 42.52 -2.87 0.00
Llph-ps2 153.57 1.24 0.00
Glns-ps1 22.44 -3.80 0.00
Gm44787 64.41 1.29 0.00
mt-Rnr2 26254.02 1.31 0.00
Wdr6 225.77 -1.20 0.00
Gm11478 37.33 -3.15 0.00
mt-Ts1 8.67 -6.48 0.00
Sult1d1 7050.73 1.23 0.00
Gm4149 26.70 -3.47 0.00
Mmp15 568.82 -1.31 0.00
Glg1 618.07 -1.06 0.00
Gm8730 38.62 -3.12 0.00
Ntn3 86.17 -1.14 0.00
mt-Nd5 112471.87 1.05 0.00
Prrc2b 786.02 -1.08 0.00
Gm16437 12.77 -3.73 0.00
Got2-ps1 50.37 -1.79 0.00
Gm4366 45.90 -2.24 0.00
Rps13-ps2 17.78 -4.34 0.00
Gem 73.48 1.06 0.00
Bnip3 9057.70 1.03 0.00
Gm10221 28.96 -2.94 0.00
ENSMUSG00000140457 645.51 1.08 0.00
Glo1-ps 38.32 -2.76 0.00
Gm6204 27.29 -3.58 0.00
Gm13611 10.64 -5.57 0.00
Zfp931 151.31 1.12 0.00
Rps16-ps2 60.07 -2.69 0.00
Gm12174 18.93 -2.94 0.00
ENSMUSG00000128633 69.82 -3.56 0.00
Cox5b-ps 30.67 -2.53 0.00
ENSMUSG00000135866 197.29 -3.57 0.00
Gabbr2 251.86 -1.54 0.00
Gm15163 32.17 -2.59 0.00
ENSMUSG00000137224 104.65 -1.90 0.00
Tpi-rs11 5.57 -5.23 0.00
Gm28661 121201.09 1.03 0.00
Foxq1 122.17 -1.44 0.00
Pgam1-ps2 21.91 -2.94 0.00
Ms4a6b 37.59 1.51 0.00
Mknk2 1424.28 -1.02 0.00
Akap17a 172.66 -1.16 0.00
Gm6548 68.88 -1.12 0.00
Fn1 17956.83 -1.21 0.00
Ap2m1-ps 47.51 -2.03 0.00
Nup210 220.88 -1.14 0.00
Zbtb42 88.86 -1.10 0.00
ENSMUSG00000135935 9.62 4.09 0.00
Gstp-ps 180.07 -3.04 0.00
Gm5805 9.69 -3.89 0.00
Gm9816 15.44 -2.76 0.00
Gm44170 57.00 -1.83 0.00
Zfp85 59.08 1.01 0.00
Gm14586 30.77 -2.86 0.00
Gm13436 25.88 -3.28 0.00
Clec7a 204.54 1.06 0.00
ENSMUSG00000126438 12.18 -3.20 0.00
Gm45774 19.92 2.48 0.00
Gm7600 12.26 -4.49 0.00
Nphs1 4.55 3.81 0.00
Abca3 921.23 -1.04 0.00
Lars2 40213.28 1.19 0.00
Uba52rt 168.94 -1.73 0.00
Gm9616 12.20 -3.39 0.00
Mfhas1 317.75 -1.18 0.00
Gm37035 168.67 -1.06 0.00
Gm9755 18.05 -2.55 0.00
Rpl23a-ps3 23.48 -2.51 0.00
2010001A14Rik 131.74 1.01 0.00
Gm9625 25.61 -2.37 0.00
Gm6344 12.16 -2.83 0.00
Gm10039 16.61 -2.85 0.00
Gm6652 235.21 -1.45 0.00
Igsf8 113.92 -1.10 0.00
Eif4a-ps4 79.49 -1.59 0.00
Rps3a2 57.75 -1.99 0.00
ENSMUSG00000130597 7.91 3.14 0.00
Ccdc148 51.30 1.06 0.00
Gm7536 93.43 -1.82 0.00
Sort1 257.10 -1.30 0.00
Gm6733 14.45 -2.93 0.00
Gm12918 62.28 -1.98 0.00
Cxcl2 7.09 2.47 0.00
ENSMUSG00000126686 56.16 1.20 0.00
Farp1 250.46 -1.02 0.00
ENSMUSG00000132604 16.21 -3.19 0.00
Sap18b 31.12 -1.94 0.00
ENSMUSG00000128869 7.74 -5.19 0.00
Rpl15-ps3 34.21 -5.43 0.00
Agbl3 115.30 1.08 0.00
Rps18-ps6 51.75 -2.31 0.00
Cadm4 220.38 -1.09 0.00
Rpl19-ps11 82.22 -1.92 0.00
Cspg5 32.16 -2.10 0.00
Rpl34-ps1 50.78 -4.66 0.00
Rps25-ps1 12.44 -3.11 0.00
Gm10874 18.42 -2.55 0.00
ENSMUSG00000123794 24.12 -1.36 0.00
Kif26b 17.55 -1.68 0.00
ENSMUSG00000143494 36.29 1.41 0.00
Rpsa-ps10 70.29 -1.99 0.00
Gm9794 60.24 -2.05 0.00
Rps18-ps5 34.58 -3.70 0.00
2810001A02Rik 158.86 1.02 0.00
Rps26-ps1 15.04 -7.28 0.00
Gm5835 22.83 -2.65 0.00
Gm5456 13.70 -4.03 0.00
Pzp 54053.75 -1.18 0.00
Gm11844 271.37 1.10 0.00
Gm57048 107.61 1.08 0.00
Glud-ps 28.87 -2.15 0.00
Rpl6l 18.42 -2.23 0.00
Gm5540 27.95 -2.41 0.00
Serpinb6b 83.41 1.04 0.00
Zfp97 134.90 1.03 0.00
4921516A02Rik 58.14 -1.80 0.00
5033403H07Rik 575.81 1.03 0.00
Lpar2 23.40 -1.88 0.00
Gm12183 21.22 -2.55 0.00
Gm12350 25.63 -2.43 0.00
Arhgef16 42.71 -1.27 0.00
Rpl7-ps7 7.91 -2.41 0.00
Rps23-ps1 41.76 -2.14 0.00
Gm379 21.93 -4.38 0.00
Nhsl3 933.22 -1.06 0.00
Rtl8a 70.46 -1.22 0.00
Tpm3-rs7 16.20 -2.22 0.00
Slc38a3 16620.44 -1.34 0.00
Wfdc17 299.80 1.15 0.00
Atp6v0c-ps2 7.13 -2.96 0.00
Gm7336 334.35 -1.05 0.00
Gm7049 12.00 -2.80 0.00
Hspe1-rs1 30.45 -2.23 0.00
ENSMUSG00000121793 83.33 -2.50 0.00
Gm16573 440.88 1.27 0.00
Ihh 42.91 -2.33 0.00
Nat1 49.55 1.01 0.00
Gm10232 11.41 -2.67 0.00
4930524O07Rik 25.51 1.17 0.00
Gm31583 1705.41 1.10 0.00
Ndufb4c 248.05 1.05 0.00
Wnk4 33.64 -1.18 0.00
Gm6180 5.82 -3.38 0.00
ENSMUSG00000121505 192.41 1.49 0.00
1700085D22Rik 24.07 1.02 0.00
ENSMUSG00000121863 146.26 1.16 0.00
Gm30784 212.29 1.17 0.00
Rpl17-ps3 37.90 -2.01 0.00
Gm32281 84.20 1.47 0.00
Gm15889 39.60 1.29 0.00
Rps19-ps6 31.72 -2.46 0.00
Cd276 47.14 -1.90 0.00
Gm5421 6.53 -3.65 0.00
Gm45507 152.92 1.34 0.00
Lnx1 12.40 -3.07 0.00
ENSMUSG00000121776 34.08 -2.24 0.00
Susd4 769.22 -1.01 0.00
ENSMUSG00000122459 27.81 1.60 0.00
Gm49190 36.83 -1.14 0.00
BC028528 23.92 1.27 0.00
Gm11964 8.74 -3.49 0.00
Cxcl14 48.69 -1.22 0.00
Gm5424 812.64 -2.00 0.00
Gm15772 21.29 -2.46 0.00
Gm6206 12.64 -2.39 0.00
Rpl14-ps1 43.81 -1.94 0.00
Faap100 79.58 -1.01 0.00
Rplp2-ps1 23.44 -2.93 0.00
Gm7666 33.37 -2.12 0.00
Rps15-ps2 6.33 -3.94 0.00
ENSMUSG00000135161 90.94 1.29 0.00
Gm5905 21.69 -2.01 0.00
Slc13a3 297.39 -1.35 0.00
Klf13 755.08 -1.10 0.00
Ftl1-ps1 415.27 -2.03 0.00
Gm10250 33.40 -2.18 0.00
Gm7730 9.25 -3.39 0.01
Gm8355 32.41 -1.65 0.01
Gm5422 11.10 -3.03 0.01
Gm8399 4.91 -3.85 0.01
Cyp1b1 17.02 1.08 0.01
Rpl36a-ps2 16.07 -2.15 0.01
Gm56543 25.67 1.21 0.01
Kpna2rt 15.04 -2.30 0.01
Rab11b-ps2 4.40 -4.42 0.01
Casp1 48.41 1.05 0.01
Gm2962 10.49 -2.66 0.01
Rpl35rt 92.16 -2.56 0.01
2810013P06Rik 155.27 1.05 0.01
Rpl31-ps8 32.16 -1.77 0.01
Ndufb4b 87.04 2.65 0.01
Smpd3 37.41 -1.71 0.01
ENSMUSG00000132147 46.32 -2.08 0.01
Gm10778 67.40 1.01 0.01
Arg2 7.33 1.85 0.01
Rpsa-ps2 7.33 -3.50 0.01
Mug2 7390.61 -1.10 0.01
Eno1b 29.58 -3.36 0.01
ENSMUSG00000125136 5.87 -2.78 0.01
Ccdc152 3315.21 1.00 0.01
Rps27a-ps2 42.09 -1.65 0.01
Gm20056 9.93 -2.31 0.01
ENSMUSG00000139771 115.89 -2.34 0.01
Gm7816 20.63 -2.02 0.01
Cyp2c23 3904.20 -1.19 0.01
Jchain 93.33 1.14 0.01
Srebf1 1786.93 -2.59 0.01
Hspd1-ps3 48.06 -1.61 0.01
Sdk2 7.97 -1.92 0.01
Chrna4 8.34 -4.71 0.01
Gm21399 46.08 -1.81 0.01
Pdxk 799.12 -1.20 0.01
Mif-ps4 6.85 -3.94 0.01
Gm5182 8.95 -3.01 0.01
Adrm1b 29.01 -2.30 0.01
Gm12744 340.15 -1.00 0.01
Cobl 240.61 -1.31 0.01
Rps10-ps1 10.28 -3.22 0.01
ENSMUSG00000132047 11.93 1.66 0.01
Gm4294 11.09 2.68 0.01
ENSMUSG00000128448 28.82 1.23 0.01
Il1b 67.35 1.43 0.01
Gm30938 28.19 1.03 0.01
Col1a1 49.78 -1.25 0.01
Gm56749 211.90 1.02 0.01
Klrb1c 11.80 1.59 0.01
Gm4459 10.44 -2.91 0.01
Dclk3 91.43 -1.43 0.01
Syt1 194.29 -1.41 0.01
Col15a1 65.40 -1.36 0.01
Dpy19l3 226.63 -2.21 0.01
Osgin1 1011.34 -1.19 0.01
Eef2k 120.28 -1.27 0.01
Gm7204 15.80 -2.04 0.01
ENSMUSG00000121608 16.68 -1.52 0.01
Gm35035 16.14 1.20 0.01
Gm57504 12.84 -1.80 0.01
Gm6863 46.39 -1.50 0.01
Cd83 47.24 1.10 0.01
Gm10053 80.81 -2.25 0.01
Gm6170 9.82 -2.95 0.01
Gm10288 85.93 -2.21 0.01

6.1.1.3 Females only

There are 271 significantly differentially expressed genes (FDR < 0.01, |log2FC| > 1) in the liver between female Cre-AAV and GFP control switch mice.

Diagnostic plots for the DE analysis

  • A histogram enriched for low p-values shows the presence of true differential expression (deviation from the uniform null), rather than an all-noise result.
  • The log(baseMean) distribution for significant genes being skewed toward moderate–high counts indicates findings are driven by well-expressed features, not low-count noise that can inflate fold-changes and p-values.
Significantly differentially expressed genes in liver
Cre-AAV and GFP control
(FDR < 0.01, |log2FC| > 1)
gene baseMean log2FoldChange padj
Gstm2-ps1 56.95 -4.18 0.00
Ftl1-ps1 616.64 -2.90 0.00
ENSMUSG00000121793 134.00 -3.25 0.00
Gm13436 37.30 -4.58 0.00
Oaz1-ps 167.06 -2.71 0.00
Gm8730 65.75 -3.92 0.00
Gm10163 44.25 -2.82 0.00
Gm5540 37.08 -3.89 0.00
Rpl35rt 153.90 -2.97 0.00
Gm14586 58.66 -3.71 0.00
Gm5452 36.99 -3.56 0.00
Rpl18-ps2 38.76 -3.75 0.00
Rpl17-ps3 81.42 -3.34 0.00
Gm11478 64.04 -3.59 0.00
Gm15427 104.00 -3.09 0.00
Gm10073 43.41 -4.19 0.00
Fmo3 6276.21 1.31 0.00
Gm10263 23.25 -5.46 0.00
Rpl34-ps1 49.54 -3.91 0.00
Mir6236 23.16 -2.93 0.00
Gm4332 46.87 -3.96 0.00
Rps19-ps6 53.97 -3.34 0.00
Tpt1-ps3 189.25 -2.44 0.00
Gm8355 57.90 -2.76 0.00
Gm9794 87.32 -2.73 0.00
Rps23-ps1 72.36 -2.55 0.00
Rps16-ps2 100.17 -2.94 0.00
ENSMUSG00000143433 31.98 -3.71 0.00
Gm9385 67.23 -2.86 0.00
Adrm1b 43.96 -3.17 0.00
Gm37273 37.17 2.03 0.00
Gm12350 43.51 -3.34 0.00
Gm4366 69.10 -2.52 0.00
Gm10232 20.55 -3.80 0.00
Glns-ps1 36.25 -3.29 0.00
Hadhb-ps 198.94 -2.09 0.00
Gm10221 48.86 -3.16 0.00
Gm45855 37.81 -2.83 0.00
Rpl28-ps1 75.11 -3.24 0.00
Rps6-ps4 180.62 -1.98 0.00
Gm15163 45.00 -2.93 0.00
Rpl19-ps11 142.75 -2.47 0.00
ENSMUSG00000131289 23.67 -3.37 0.00
Eif3j2 74.10 -2.31 0.00
Gm6863 89.31 -2.30 0.00
Hspe1-rs1 46.65 -3.01 0.00
Gm6548 95.94 -1.41 0.00
Gm21399 69.32 -2.40 0.00
Gm9826 188.18 -2.47 0.00
Gm7658 17.91 -3.44 0.00
Gm7049 25.55 -3.29 0.00
Hspb1 512.58 -1.63 0.00
Gstp-ps 26.40 -3.63 0.00
Glo1-ps 47.48 -2.77 0.00
Rpsa-ps10 100.33 -2.63 0.00
Gm7536 145.67 -2.44 0.00
Gm6789 131.70 -1.96 0.00
Gm44442 385.21 -1.78 0.00
Rps3a2 99.47 -2.63 0.00
Cd36 5420.42 -1.48 0.00
ENSMUSG00000121777 752.26 -1.78 0.00
Gm5422 15.87 -4.04 0.00
Rps10-ps1 23.45 -4.55 0.00
Mif-ps4 12.40 -5.92 0.00
Gm10250 58.21 -2.92 0.00
Gm7600 21.70 -3.30 0.00
Gm10288 146.38 -3.17 0.00
Gm4459 20.19 -3.78 0.00
Mpv17l 486.85 1.06 0.00
Gm5560 27.77 -2.85 0.00
Gm9625 29.60 -3.04 0.00
Gm16439 47.51 -2.76 0.00
Gm9816 16.50 -3.41 0.00
Gm8566 142.36 -3.46 0.00
Gm12251 19.57 -3.25 0.00
Eef2-ps2 29.18 -3.68 0.00
Gm2962 12.40 -3.62 0.00
Rps18-ps3 29.37 -3.66 0.00
Gm4149 43.56 -2.95 0.00
Rpl9-ps4 28.55 -2.77 0.00
Gm5835 29.22 -2.71 0.00
Rps24-ps3 46.03 -2.80 0.00
Gm9755 22.56 -3.60 0.00
Gpi-ps 21.72 -3.29 0.00
ENSMUSG00000135866 314.47 -4.00 0.00
Ccdc148 100.86 1.27 0.00
Gm12174 36.76 -2.96 0.00
Hspd1-ps3 66.43 -2.11 0.00
Gm5805 19.10 -4.39 0.00
Gm13680 20.13 -2.98 0.00
Rpl23a-ps3 45.95 -2.71 0.00
Gm13461 17.26 -3.21 0.00
Gm16437 16.83 -3.74 0.00
Gm5456 18.07 -3.47 0.00
Uba52rt 236.73 -1.95 0.00
Rpl7-ps7 19.25 -2.92 0.00
Rps18-ps5 56.92 -4.10 0.00
Gm13611 14.75 -5.33 0.00
Rps13-ps1 47.05 -2.84 0.00
Gm10819 10.99 -3.91 0.00
Glud-ps 47.34 -2.63 0.00
Gm6652 306.73 -1.52 0.00
Vcp-rs 71.89 -3.61 0.00
Rps27a-ps2 69.59 -2.00 0.00
Gm15772 31.91 -2.95 0.00
Gm10252 13731.24 1.35 0.00
Gm32202 39.44 1.89 0.00
mt-Ts1 7.22 -6.66 0.00
Cox5b-ps 43.28 -2.69 0.00
ENSMUSG00000139771 234.92 -3.23 0.00
Rpl14-ps1 66.31 -1.99 0.00
ENSMUSG00000121783 636.13 -1.27 0.00
Eno1b 47.81 -4.09 0.00
Mrpl23-ps1 21.13 -3.21 0.00
Gm9493 42.99 -2.52 0.00
Gm9892 24.38 -2.20 0.00
Gm11964 12.28 -4.43 0.00
Gm6170 14.82 -2.97 0.00
Gm30505 109.57 1.24 0.00
Gm2223 30.06 -2.31 0.00
Gm12346 27.63 -2.76 0.00
Gm49909 875.96 1.01 0.00
Slc27a1 824.35 -1.35 0.00
Rpl17-ps10 95.65 -2.20 0.00
Gm12183 28.63 -2.53 0.00
Slc41a2 157.56 -1.29 0.00
Slc16a13 64.44 -1.57 0.00
Sap18b 44.77 -2.37 0.00
Got2-ps1 65.39 -1.80 0.00
ENSMUSG00000130204 55.25 -1.73 0.00
Sult2a6 42.55 -2.41 0.00
Btf3-ps1 27.18 -2.25 0.00
Eif4a-ps4 128.04 -1.74 0.00
Gm10874 24.59 -2.35 0.00
Gm7666 47.96 -2.69 0.00
Rpl6l 25.18 -1.87 0.00
Pam16l 14.01 -3.09 0.00
Rps15-ps2 9.63 -3.75 0.00
Wdr89 106.60 -1.44 0.00
ENSMUSG00000123407 9.84 -4.03 0.00
Gm10039 24.72 -2.56 0.00
ENSMUSG00000137224 150.92 -1.45 0.00
Rps2-ps10 49.08 -9.44 0.00
H2ac19 841.06 -1.47 0.00
ENSMUSG00000121784 164.41 -1.53 0.00
ENSMUSG00000122915 16.17 -4.17 0.00
ENSMUSG00000141422 514.55 -1.11 0.00
Gm12992 82.45 -1.48 0.00
ENSMUSG00000134769 25.99 2.55 0.00
Rpl31-ps8 56.84 -1.91 0.00
Acaa1b 33296.38 -1.11 0.00
Gm13835 107.39 -1.73 0.00
Rpl36-ps12 56.57 -2.09 0.00
Vnn1 7032.14 -1.06 0.00
Sema5b 51.77 -1.38 0.00
ENSMUSG00000141528 28.43 -1.88 0.00
ENSMUSG00000132147 90.49 -3.00 0.00
Actr3-ps 15.76 -2.45 0.00
Rps10-ps2 59.45 -1.87 0.00
Gm6136 75.47 -1.81 0.00
Ntn3 107.00 -1.07 0.00
Ndufb4c 333.56 1.07 0.00
Gm13456 618.96 -2.17 0.00
Gm15519 13.55 -3.08 0.00
Rps26-ps1 22.57 -8.32 0.00
Gm10222 7355.03 2.47 0.00
Rps18-ps6 114.18 -2.95 0.00
ENSMUSG00000128633 117.00 -3.16 0.00
Tmem238 406.11 -1.14 0.00
Map2k6 141.58 1.55 0.00
Gm56542 154.02 4.69 0.00
Gm5436 16.98 -3.18 0.00
Rps27rt 231.43 -2.31 0.00
ENSMUSG00000132256 11.62 -2.95 0.00
Gm6055 10.53 -2.85 0.00
Gm8203 7.28 -3.74 0.00
Gm57204 53.81 1.36 0.00
ENSMUSG00000126438 17.29 -3.18 0.00
Scand1 349.22 -1.04 0.00
Gm10069 37.29 -1.15 0.00
Serpina12 101.97 1.58 0.00
Rps25-ps1 19.98 -3.04 0.00
Akap17a 247.85 -1.28 0.00
Gm6204 37.46 -3.99 0.00
Serpina1e 3916.20 3.50 0.00
ENSMUSG00000125175 27.91 -2.60 0.00
Atp5pb-ps 42.85 -1.78 0.00
Gm2225 12.96 -2.92 0.00
ENSMUSG00000121597 26.68 7.82 0.00
Tmed2b 24.40 -1.77 0.00
Gm7816 24.75 -2.49 0.00
Hspa1b 174.94 -1.05 0.00
ENSMUSG00000138136 353.63 -1.09 0.00
Gm14097 593.36 1.34 0.00
Cyp26b1 425.37 -1.05 0.00
AK157302 8.20 -3.33 0.00
Gm6733 15.17 -2.53 0.00
Gm12918 116.30 -2.78 0.00
Gm9616 16.44 -2.70 0.00
Fosb 36.79 2.34 0.00
Cxcl1 101.56 1.65 0.00
Cirbp 685.58 1.04 0.00
Gm10157 33.29 -1.96 0.00
Sco2 2550.79 -1.14 0.00
Gm20634 128.50 -1.28 0.00
Ap2m1-ps 60.54 -1.82 0.00
Psma5-ps 25.30 -2.46 0.00
Gm7730 11.76 -3.49 0.00
Bhmt1b 1218.37 -2.56 0.00
Gm29216 9425.74 -3.84 0.00
Atp2b2 77.71 -1.61 0.00
Gm7204 21.60 -2.07 0.00
Gm49077 131.11 1.46 0.00
ENSMUSG00000133704 29.41 -2.15 0.00
Gm15542 61.77 -1.27 0.00
Upp2 4131.01 2.22 0.00
Gm12669 36.97 -1.58 0.00
Gm28661 153977.94 1.04 0.00
Rps15a-ps7 19.57 -2.73 0.00
Hmgb1-ps3 6.67 5.20 0.00
Gm12966 17.32 -2.39 0.00
Mapk15 63.22 -1.11 0.00
Gm10053 127.87 -2.32 0.00
Chpf 87.92 -1.17 0.00
Gm7336 414.06 -1.17 0.00
Gm6180 8.06 -3.52 0.00
Nudc-ps1 7.33 -3.57 0.00
Gm45053 31.53 -1.30 0.00
Serinc2 251.39 -1.31 0.00
Nrtn 28.55 -1.73 0.00
Rpl10a-ps1 125.72 -1.32 0.00
Pgam1-ps2 25.24 -2.32 0.00
Gm2614 12.83 -3.24 0.00
Gm6123 12.23 -2.66 0.00
mt-Nd5 141867.14 1.02 0.00
Gm5499 5.66 -3.25 0.00
Llph-ps2 215.84 1.00 0.01
Etnppl 2484.41 1.02 0.01
Rpl9-ps6 275.76 -1.89 0.01
Rbm3 1912.51 1.19 0.01
Fam83g 51.21 -1.10 0.01
Rasl2-9 43.90 1.05 0.01
Gm26608 56.34 1.07 0.01
Gm5182 11.42 -2.61 0.01
Gm10095 23.09 -1.68 0.01
Gm10036 17.84 -2.56 0.01
Kansl2-ps 7.04 -2.59 0.01
Gm10335 57.45 -1.12 0.01
Rab11b-ps2 5.19 -3.92 0.01
ENSMUSG00000129688 19.14 -1.79 0.01
2010002M09Rik 40.36 1.04 0.01
Scd1 21373.27 1.24 0.01
Tpm3-rs7 22.95 -1.76 0.01
Lilrb4b 118.38 1.19 0.01
Gm16098 36.18 1.76 0.01
ENSMUSG00000125136 10.78 -2.34 0.01
Dmbt1 107.15 5.92 0.01
Rpl3-ps1 120.99 -1.31 0.01
Ahcyl 1584.59 -1.71 0.01
Gm14494 16.31 -2.33 0.01
Gm4202 8.76 -2.88 0.01
ENSMUSG00000121655 26.14 -2.11 0.01
ENSMUSG00000139337 94.84 1.12 0.01
ENSMUSG00000125715 38.36 -1.28 0.01
Erdr1y 232.88 -1.07 0.01
Gm9512 21.09 -2.03 0.01
Pdcd5-ps 16.91 -1.55 0.01
Hectd2 84.76 -1.21 0.01
Gm53019 30.36 1.65 0.01
Gm45753 8.56 3.14 0.01
Gm2999 11.02 -2.85 0.01

6.1.1.4 Common DEGs in males and females

Differential expression analysis comparing Cre-AAV and GFP control groups in liver identified a large number of significantly altered transcripts (FDR < 0.01, |log₂FC| > 1). To focus on robust and biologically relevant signals, we intersected DEGs detected in both male and female mice.

There were 119 common DEGs shared in male and females. The majority corresponded to ribosomal and uncharacterized pseudogenes, reflecting global transcriptional perturbations rather than specific pathway activation.

gene
Gm16437
Gm9755
Ccdc148
Gm5422
Adrm1b
Gm6863
Rpl14-ps1
Rpsa-ps10
Gm8566
Gm7204
Gm5540
Gm6180
Rpl18-ps2
Gm7536
Tpm3-rs7
Rpl28-ps1
Hspd1-ps3
Rps27a-ps2
Gm10053
Eno1b
Rps26-ps1
Gm10073
Rps16-ps2
Rps10-ps1
Sap18b
Gm5805
Gm15772
Ftl1-ps1
Rps3a2
Gm8730
mt-Ts1
mt-Nd5
Gm13611
Gm12918
Gm10263
Rps25-ps1
Gm7666
Gm10221
Rpl31-ps8
Gm10232
Uba52rt
Rpl34-ps1
Gm10250
Rps18-ps6
Gm10288
Rps15-ps2
Gm4149
Glo1-ps
Gm10874
Rpl23a-ps3
Rpl35rt
Gm7336
Cox5b-ps
Gm12174
Got2-ps1
Gm11964
Rpl19-ps11
Ap2m1-ps
Pgam1-ps2
Glns-ps1
Gm12183
Eef2-ps2
Gm7816
Vcp-rs
Llph-ps2
Ndufb4c
Gm14586
Gm4459
Mif-ps4
Gm13436
Gm11478
Gm6733
Gm15163
Gm9816
Gm2962
Rpl6l
Gm10039
Gm6548
Gm8355
Gm5456
Gm21399
Gm12350
Rab11b-ps2
Rps19-ps6
Gm9625
Gm6652
Gm6170
Rps23-ps1
Eif4a-ps4
Gm5835
Gm28661
Gstp-ps
Gm6204
Gm4332
Rpl7-ps7
Gm9794
Gstm2-ps1
Gm4366
Glud-ps
Gm7600
Gm7730
Gm45855
Gm5182
Rps18-ps5
Gm7049
Rpl17-ps3
Gm9616
Ntn3
Hspe1-rs1
Akap17a
ENSMUSG00000121793
ENSMUSG00000125136
ENSMUSG00000126438
ENSMUSG00000128633
ENSMUSG00000132147
ENSMUSG00000135866
ENSMUSG00000137224
ENSMUSG00000139771
ENSMUSG00000143433

Filtering out pseudogenes, unannotated loci (Gm*), mitochondrial genes, and Ensembl-only identifiers yielded 11 high-confidence nuclear genes consistently dysregulated across sexes, representing the shared hepatic response to Cre-mediated ApoE4→ApoE2 conversion.

Ccdc148, Adrm1b, Tpm3-rs7, Eno1b, Sap18b, Uba52rt, Vcp-rs, Ndufb4c, Ntn3, Hspe1-rs1, Akap17a

Importantly, the absence of strong pro-inflammatory or lipid metabolism signatures indicates that the Cre-AAV–driven ApoE4→ApoE2 conversion did not induce overt hepatic stress or metabolic disruption, consistent with physiological tolerance to ApoE2 expression in liver.

6.1.2 Brain

6.1.2.1 All mice (male and females)

There are 369 significantly differentially expressed genes (FDR < 0.01, |log2FC| > 1) in the brain between Cre-AAV and GFP control switch mice.

Diagnostic plots for the DE analysis

  • A histogram enriched for low p-values shows the presence of true differential expression (deviation from the uniform null), rather than an all-noise result.
  • The log(baseMean) distribution for significant genes being skewed toward moderate–high counts indicates findings are driven by well-expressed features, not low-count noise that can inflate fold-changes and p-values.
Significantly differentially expressed genes in brain
Cre-AAV and GFP control
(FDR < 0.01, |log2FC| > 1)
gene baseMean log2FoldChange padj
Gm4149 32.14 -3.47 0.00
Rps6-ps4 114.03 -1.93 0.00
Rps13-ps1 29.45 -3.74 0.00
Rpl35rt 127.39 -3.71 0.00
Gm9385 44.16 -3.00 0.00
Gm15427 62.94 -3.25 0.00
Gm56350 25.27 -23.45 0.00
Rps18-ps5 21.51 -4.78 0.00
Cox5b-ps 36.04 -2.69 0.00
Rpl14-ps1 54.61 -2.58 0.00
Rpsa-ps10 73.01 -3.03 0.00
Rps19-ps6 39.57 -3.65 0.00
Gm10288 95.03 -3.25 0.00
Gm14586 31.34 -3.37 0.00
Gm11478 43.13 -3.64 0.00
Gm49388 8.17 -22.20 0.00
Rpl17-ps3 51.71 -3.08 0.00
Rpl17-ps10 78.29 -2.77 0.00
Rps23-ps1 47.87 -2.75 0.00
Rpl19-ps11 100.00 -2.77 0.00
Gm6560 71.28 -2.25 0.00
Rpl28-ps1 38.67 -3.04 0.00
Rps24-ps3 27.56 -3.25 0.00
ENSMUSG00000121779 67.38 -1.43 0.00
Gm8226 77.93 -1.92 0.00
Gm10073 42.07 -3.91 0.00
Rps16-ps2 56.86 -3.36 0.00
Gm15772 27.73 -3.17 0.00
Rps3a2 68.79 -2.80 0.00
Rpl9-ps6 207.66 -2.48 0.00
Rpl34-ps1 58.67 -5.61 0.00
ENSMUSG00000143433 23.97 -3.95 0.00
Rpl3-ps1 177.92 -1.92 0.00
Gm8566 19.88 -3.26 0.00
Rpl36a-ps2 19.81 -2.69 0.00
Gm7308 39.17 -2.16 0.00
ENSMUSG00000121793 82.31 -3.29 0.00
Eno1b 46.82 -3.11 0.00
Fbxl15 309.95 -1.04 0.00
Rps27a-ps2 47.51 -2.21 0.00
Uba52rt 146.27 -2.28 0.00
Gm9794 53.70 -2.40 0.00
Gm5436 13.72 -3.83 0.00
Gm13456 185.31 -2.33 0.00
ENSMUSG00000139771 140.96 -3.10 0.00
Gm9493 32.22 -2.97 0.00
Gm11223 39.02 -2.19 0.00
Nme3 427.94 -1.08 0.00
Gm6180 26.71 -2.47 0.00
Gm10053 137.06 -2.69 0.00
Gm6789 40.04 -2.08 0.00
ENSMUSG00000128633 87.85 -4.13 0.00
ENSMUSG00000137224 81.76 -1.73 0.00
Gm4332 27.83 -4.19 0.00
Rps10-ps2 42.55 -2.15 0.00
Gm10052 36.46 -1.53 0.00
Gm22009 108.53 3.86 0.00
Rpl23a-ps3 36.22 -2.72 0.00
Gm16437 13.55 -3.08 0.00
Nicol1 359.05 -1.16 0.00
ENSMUSG00000132604 23.26 -3.53 0.00
Gm9816 28.68 -2.67 0.00
Gm4366 80.72 -2.31 0.00
Gm8730 22.80 -3.64 0.00
Gm12254 19.52 -2.37 0.00
Nrtn 70.42 -1.71 0.00
Gm5499 26.96 -2.38 0.00
Rpl31-ps8 54.28 -2.07 0.00
Gm8203 16.15 -3.22 0.00
Rps15a-ps7 15.30 -3.26 0.00
ENSMUSG00000121655 13.35 -2.70 0.00
ENSMUSG00000121784 141.92 -1.99 0.00
Rps25-ps1 13.20 -4.32 0.00
Rpl18-ps2 19.06 -3.97 0.00
Rpl10a-ps1 64.06 -1.67 0.00
Hadhb-ps 26.49 -1.66 0.00
Gm10250 41.82 -2.47 0.00
Nudc-ps1 12.44 -2.73 0.00
1810049J17Rik 13.52 -4.30 0.00
Gm12892 86.68 -2.36 0.00
Gm8355 58.54 -1.68 0.00
Gm37035 222.55 -1.13 0.00
Pgam1-ps2 69.18 -2.69 0.00
Sap18b 29.87 -2.23 0.00
Gm4202 64.78 -1.76 0.00
Gm10221 21.69 -3.22 0.00
Gm12918 95.27 -3.02 0.00
Rps27rt 127.14 -2.80 0.00
Gm7536 94.72 -2.57 0.00
ENSMUSG00000138427 13.96 -3.59 0.00
Gm13611 9.98 -5.73 0.00
ENSMUSG00000121777 294.76 -1.79 0.00
Gm7600 16.41 -4.28 0.00
Aldoart1 15.50 -3.42 0.00
Glns-ps1 27.12 -2.70 0.00
Oaz1-ps 63.61 -2.53 0.00
Gm6863 46.20 -2.13 0.00
Ube2srt 20.90 -2.67 0.00
Gm13436 23.63 -4.15 0.00
Eef2-ps2 16.93 -3.03 0.00
Fam221b 58.28 -1.23 0.00
Scand1 368.57 -1.11 0.00
mt-Co2 52612.16 -1.22 0.00
Actr3-ps 17.91 -2.37 0.00
Atp6v0c-ps2 39.07 -1.97 0.00
Gm4459 11.08 -3.21 0.00
Gm12346 129.10 -1.35 0.00
Ap2m1-ps 151.10 -1.31 0.00
Ldhb-ps 44.98 -2.14 0.00
Vcp-rs 48.51 -1.74 0.00
Rps18-ps6 37.62 -3.38 0.00
Rps7-ps3 49.39 -2.96 0.00
Gm10263 12.83 -4.54 0.00
Pcsk1n 9530.38 -1.08 0.00
Gm2225 13.47 -3.67 0.00
Gm9625 22.29 -1.89 0.00
Gm5805 13.06 -4.38 0.00
ENSMUSG00000121783 439.67 -1.56 0.00
Gm45855 12.83 -3.98 0.00
ENSMUSG00000131289 12.38 -2.49 0.00
Rpl6l 20.09 -2.25 0.00
Gm12251 11.83 -3.19 0.00
Tmem238 65.41 -1.09 0.00
Eif4a-ps4 75.56 -1.52 0.00
Gpi-ps 57.80 -2.40 0.00
Gm7666 20.16 -3.03 0.00
Gm6204 28.93 -3.86 0.00
H3c15 39.97 -1.23 0.00
Gm6136 52.82 -1.72 0.00
Gm14150 18.33 -2.84 0.00
Gstp-ps 13.48 -3.28 0.00
Gm12174 18.56 -3.10 0.00
Gm14121 11.27 -2.67 0.00
Tpt1-ps3 57.66 -2.39 0.00
Rps26-ps1 14.10 -7.13 0.00
Prkcz2 28.87 -2.16 0.00
Hspe1-rs1 14.15 -3.22 0.00
Gm8399 30.52 -2.23 0.00
Gm10163 45.93 -1.84 0.00
Gm2614 8.44 -4.27 0.00
4632415L05Rik 13.95 -7.12 0.00
Rpl7-ps7 6.61 -3.22 0.00
Tmsb10b 24.99 -1.64 0.00
Rps15-ps2 9.70 -3.34 0.00
Mif-ps4 10.76 -4.49 0.00
Gm12481 40.91 -6.50 0.00
Rps10-ps1 12.85 -4.16 0.00
Ftl1-ps1 44.16 -2.55 0.00
H2ac19 199.63 -1.47 0.00
Yjefn3 120.58 -1.07 0.00
Gm12183 38.98 -1.95 0.00
Gm3571 7.69 -4.32 0.00
Gm2223 19.27 -1.68 0.00
Gm37530 11.01 1.78 0.00
Gm5844 26.21 -1.61 0.00
Gm6344 9.56 -3.51 0.00
Gm2999 17.93 -2.75 0.00
Gm10039 16.02 -2.49 0.00
Gm5526 12.57 -5.43 0.00
Erhrt-ps 12.10 -3.12 0.00
Gm5421 16.50 -2.26 0.00
Gm16439 8.40 -3.03 0.00
Gm13461 15.16 -2.46 0.00
Rn7s1 495.73 1.82 0.00
Gm5835 23.57 -2.03 0.00
Rplp2-ps1 21.59 -4.75 0.00
Gm13835 42.67 -1.70 0.00
Gm9616 13.86 -2.87 0.00
Gm14494 12.60 -2.30 0.00
Gm10036 12.12 -3.46 0.00
Adrm1b 18.73 -2.25 0.00
Gm5424 12.44 -2.38 0.00
ENSMUSG00000123407 4.95 -4.39 0.00
Rpl37rt 29.84 -7.02 0.00
Gstm2-ps1 9.80 -3.48 0.00
Btf3-ps1 15.43 -2.32 0.00
Sms-ps 15.42 -1.90 0.00
Rpl36-ps12 24.82 -2.34 0.00
Rab11b-ps2 13.30 -2.63 0.00
Rn7sk 450.20 1.57 0.00
Gm12350 15.50 -2.78 0.00
Gm15519 5.84 -3.34 0.00
Atp5pb-ps 19.77 -1.93 0.00
Tpm3-rs7 19.00 -1.81 0.00
Gm37811 50.18 -1.38 0.00
ENSMUSG00000132287 16.47 -2.92 0.00
ENSMUSG00000123149 27.17 -2.06 0.00
Gm45051 16.53 -1.45 0.00
Nutf2-ps1 32.77 -1.47 0.00
Gm12966 17.05 -1.80 0.00
Ube2n-ps1 15.71 -2.43 0.00
Gm9531 12.99 -2.19 0.00
Rpl9-ps4 21.85 -3.15 0.00
Gm13680 10.57 -2.12 0.00
Ahcyl 13.84 -2.52 0.00
Gm10819 15.69 -2.49 0.00
Mrpl23-ps1 14.76 -2.90 0.00
Gm11964 5.62 -3.98 0.00
Gm37899 14.98 1.90 0.00
Cdk2ap1rt 40.72 -1.61 0.00
Pam16l 10.68 -2.71 0.00
Ywhaq-ps3 30.93 -1.93 0.00
Gm3724 12.50 -2.01 0.00
Btf3l4b 31.53 -2.28 0.00
Kansl2-ps 10.70 -2.36 0.00
Gm21399 6.10 -2.50 0.00
Gm7658 9.90 -2.75 0.00
B020010K11Rik 32.49 -3.15 0.00
Eef1a1-ps1 26.19 -1.44 0.00
Kcng3 23.69 1.18 0.00
Impdh2-ps 9.41 -2.34 0.00
ENSMUSG00000138717 17.49 -2.13 0.00
Cdr1 106.41 1.26 0.00
APOE 44215.72 2.47 0.00
Tpi-rs11 10.88 -3.50 0.00
Gm44442 131.88 -1.55 0.00
Gm5422 13.67 -2.32 0.00
Gm56991 57.98 -1.35 0.00
Oxt 157.95 -1.75 0.00
Gm9824 27.66 -1.55 0.00
Mrip-ps 12.64 -1.70 0.00
Avp 257.42 -1.45 0.00
ENSMUSG00000126438 6.97 -3.36 0.00
AK157302 17.49 -1.91 0.00
Gm5905 16.17 -2.68 0.00
9530059O14Rik 24.78 1.47 0.00
Rps13-ps2 19.30 -2.30 0.00
Gchfr 23.10 -1.48 0.00
Gm12669 25.23 -1.35 0.00
Gm6170 5.19 -3.97 0.00
Gm5560 8.77 -2.53 0.00
Psma5-ps 10.66 -2.59 0.00
Gm15421 12.70 -2.30 0.00
ENSMUSG00000137056 10.92 -2.24 0.00
Grin2b 5926.08 1.07 0.00
Gm21986 62.79 -1.93 0.00
Gm49521 27.14 1.24 0.00
Pomc 154.81 -2.67 0.00
Gm6055 10.81 -2.72 0.00
Malat1 13736.97 1.45 0.00
Gm7730 4.22 -4.23 0.00
Rpl15-ps3 42.98 -3.78 0.00
Gm7816 18.63 -1.65 0.00
mt-Ts1 6.56 -3.77 0.00
Gm10642 38.71 -1.36 0.00
Gm5456 3.59 -4.53 0.00
Eif3j2 24.77 -1.62 0.00
ENSMUSG00000140944 13.05 -1.97 0.00
ENSMUSG00000141748 78.11 -1.52 0.00
A730035I17Rik 31.38 -1.40 0.00
Amn 100.83 -1.01 0.00
Gm50322 18.27 1.10 0.00
Glo1-ps 6.45 -2.76 0.00
Gm16105 95.52 1.04 0.00
Gm2962 4.92 -2.61 0.00
ENSMUSG00000123314 68.66 -1.09 0.00
Tcea1-ps1 10.64 -1.41 0.00
Amhr2 17.15 -1.05 0.00
ENSMUSG00000125669 11.96 -2.05 0.00
Gm6477 11.68 -1.77 0.00
Gm42583 21.36 1.62 0.00
Gh 57.81 -4.88 0.00
Gm14703 210.00 -2.07 0.00
Gm10232 9.85 -1.80 0.00
ENSMUSG00000132256 5.19 -3.45 0.00
ENSMUSG00000127515 11.39 -1.65 0.00
ENSMUSG00000128869 20.90 -2.75 0.00
Hba-a1 291.47 -1.78 0.00
ENSMUSG00000136525 45052.78 1.65 0.00
Gm57848 42.57 1.03 0.00
ENSMUSG00000130204 99.69 -1.42 0.00
1700034P13Rik 48.86 1.23 0.00
Gm37345 28.47 1.02 0.00
Gm56769 26.66 -1.46 0.00
Gm56901 11.42 1.25 0.00
Kcnmb4os1 37.87 -2.01 0.00
Hspd1-ps3 17.85 -1.41 0.00
1600020E01Rik 193.78 -1.04 0.00
ENSMUSG00000133032 10.57 1.40 0.00
Gm9826 2.20 -3.79 0.00
ENSMUSG00000136970 26.45 -1.12 0.00
Pabpc1l2b 14.87 -5.99 0.00
Col6a5 12.15 1.32 0.00
Gm10335 52.17 -1.10 0.00
Rpph1 21.69 1.50 0.00
Gm14089 47.65 -2.82 0.00
Gm20431 96.78 -5.57 0.00
Gm5182 16.83 -1.15 0.00
ENSMUSG00000125136 20.47 -1.22 0.00
Gm11537 18.77 -1.19 0.00
Dhx58os 15.30 -1.03 0.00
Rpsa-ps2 7.29 -2.32 0.00
Hbb-bs 758.55 -1.64 0.00
Gm11175 14.70 -1.55 0.00
S1pr4 17.52 -1.20 0.00
Tektip1 34.53 -1.03 0.00
Gm9755 9.47 -1.96 0.00
Gm9761 19.19 -1.37 0.00
Pagr1a 46.21 -2.49 0.00
Gm43062 10.51 1.24 0.00
ENSMUSG00000121782 5.81 -2.63 0.00
Crygn 5.49 -1.91 0.00
Gm3226 13.86 -1.69 0.00
Gm9892 17.12 -1.61 0.00
Gm49518 5.94 1.89 0.00
Hspb1 196.57 -1.07 0.00
ENSMUSG00000132147 10.36 -2.13 0.00
Gm3375 14.85 -1.79 0.00
ENSMUSG00000133162 13.07 1.31 0.00
Gm37123 6.85 1.57 0.00
ENSMUSG00000121445 18.05 -1.01 0.00
Gm5452 5.28 -2.42 0.00
Hba-a2 434.02 -1.56 0.00
ENSMUSG00000121644 17.04 -1.32 0.00
Mypopos 13.49 1.32 0.00
Rn18s-rs5 224935.62 1.01 0.00
ENSMUSG00000129048 29.07 1.45 0.00
Arhgap27os2 12.87 -1.50 0.00
Tbxa2r 17.92 -1.16 0.00
Dnajb6-ps 10.44 -1.69 0.00
Gm56672 25.08 -2.34 0.00
ENSMUSG00000122915 11.94 -2.54 0.00
ENSMUSG00000143322 41.37 -1.21 0.00
Gm15163 3.41 -2.83 0.00
ENSMUSG00000123794 23.61 -1.69 0.00
ENSMUSG00000131217 22.07 -1.59 0.00
Gm6206 19.97 -1.09 0.00
Misp3 14.40 -1.07 0.00
ENSMUSG00000138136 22.32 -1.18 0.00
Kpna2rt 7.61 -2.46 0.00
Glud-ps 9.86 -1.77 0.00
Gm4735 47.74 -3.79 0.00
ENSMUSG00000121727 11.48 -3.87 0.00
Gm2423 22.85 -1.52 0.00
ENSMUSG00000135265 23.13 2.31 0.00
Gm28439 538.39 1.30 0.00
St8sia3os 13.20 -1.22 0.00
Gm43843 35.92 1.08 0.00
Usp50 9.96 -1.37 0.00
Gm6733 6.18 -1.76 0.00
Hbb-bt 117.49 -1.61 0.00
ENSMUSG00000141875 22.21 1.21 0.00
Gm15501 20.32 -3.02 0.00
Gm47956 12.70 1.06 0.00
Gm14308 112.15 -1.66 0.00
Gm26621 10.47 1.33 0.00
Scp2-ps2 6.07 -2.54 0.00
Gm13066 16.76 -3.05 0.00
Rps2-ps10 10.87 -6.76 0.00
Or7d10 10.09 -1.65 0.00
Rps18-ps3 5.71 -2.88 0.00
Fev 8.82 -1.80 0.00
Ltf 8.03 -1.94 0.00
Calhm6 5.37 -1.46 0.00
Gm49378 27.78 1.83 0.00
Bc1 6314.60 -1.45 0.01
Gm6682 12.08 -2.08 0.01
Tph2 247.79 -1.35 0.01
ENSMUSG00000141850 7.71 -1.80 0.01
Gm10874 12.34 -1.45 0.01
Rab7-ps1 12.61 -1.13 0.01
Mir6236 17.83 -1.13 0.01
Gm17167 44.02 2.67 0.01
Fam167b 7.39 -1.30 0.01
Slc6a4 114.56 -1.48 0.01
Gm7049 6.23 -2.02 0.01
Atp4a 10.03 -1.12 0.01
ENSMUSG00000130848 9.13 1.24 0.01
Gm9512 4.86 -1.54 0.01

6.1.2.2 Males only

There are 244 significantly differentially expressed genes (FDR < 0.01, |log2FC| > 1) in the brain between Cre-AAV and GFP control switch mice.

Diagnostic plots for the DE analysis

  • A histogram enriched for low p-values shows the presence of true differential expression (deviation from the uniform null), rather than an all-noise result.
  • The log(baseMean) distribution for significant genes being skewed toward moderate–high counts indicates findings are driven by well-expressed features, not low-count noise that can inflate fold-changes and p-values.
Significantly differentially expressed genes in brain
Cre-AAV and GFP control
(FDR < 0.01, |log2FC| > 1)
gene baseMean log2FoldChange padj
Gm56350 21.63 -22.39 0.00
Gm14089 41.39 -6.09 0.00
Rps13-ps1 29.93 -3.77 0.00
Rps6-ps4 111.46 -1.91 0.00
Gm13436 21.56 -5.40 0.00
Rpl14-ps1 53.57 -2.43 0.00
Rpl36a-ps2 20.29 -3.18 0.00
Gm4149 28.38 -3.65 0.00
Gm6180 28.51 -2.81 0.00
Rpl23a-ps3 38.11 -2.78 0.00
Rpsa-ps10 73.52 -3.15 0.00
Gm14586 32.11 -3.36 0.00
Gm8566 20.28 -3.84 0.00
Gm7308 39.76 -2.18 0.00
Nrtn 67.92 -1.70 0.00
Ftl1-ps1 39.87 -2.59 0.00
Rps3a2 68.11 -2.81 0.00
Rps18-ps5 20.63 -4.20 0.00
Rps27a-ps2 47.23 -2.22 0.00
Sap18b 28.91 -2.35 0.00
Gm10288 88.85 -3.43 0.00
Gm49521 25.94 1.64 0.00
Rps19-ps6 40.64 -3.52 0.00
Cox5b-ps 36.04 -2.45 0.00
Gm8203 16.15 -3.98 0.00
Gm9816 30.43 -2.93 0.00
Gh 843.07 -10.52 0.00
Rpl17-ps10 81.68 -2.82 0.00
Ube2srt 18.59 -2.95 0.00
Rpl35rt 119.88 -3.71 0.00
ENSMUSG00000121793 76.27 -3.64 0.00
Rpl34-ps1 79.62 -6.35 0.00
Rpl10a-ps1 61.21 -1.82 0.00
Gm15427 66.61 -3.17 0.00
Aldoart1 15.23 -4.09 0.00
Gm15772 25.37 -3.13 0.00
H2ac19 178.17 -1.35 0.00
Kcnmb4os1 36.92 -2.68 0.00
Gm12918 100.86 -3.00 0.00
Gm12254 20.16 -2.62 0.00
ENSMUSG00000121779 61.59 -1.29 0.00
Gm5436 13.85 -3.91 0.00
Prkcz2 29.28 -2.60 0.00
Gm11223 40.44 -2.20 0.00
Gm9385 43.98 -3.23 0.00
Gm8226 78.84 -1.91 0.00
Rps15a-ps7 14.61 -3.49 0.00
Gm8355 60.66 -1.76 0.00
ENSMUSG00000143433 23.78 -3.48 0.00
ENSMUSG00000137224 73.06 -1.64 0.00
Fbxl15 301.62 -1.01 0.00
Amn 99.96 -1.17 0.00
Atp5pb-ps 20.84 -2.55 0.00
Nme3 406.83 -1.08 0.00
Gm4332 28.61 -4.64 0.00
Gm38883 15.44 -4.59 0.00
Gm6789 40.74 -1.99 0.00
Hadhb-ps 23.81 -1.92 0.00
Gm8730 23.56 -3.20 0.00
Gm10052 34.15 -1.48 0.00
Gm10073 42.10 -3.92 0.00
Rpl9-ps6 205.98 -2.51 0.00
Gm10163 42.91 -2.14 0.00
Rpl28-ps1 39.83 -3.43 0.00
Gm11478 40.63 -3.68 0.00
Gm7600 15.57 -4.34 0.00
Ywhaq-ps3 28.89 -2.66 0.00
Gm9616 12.73 -3.42 0.00
ENSMUSG00000124434 20.26 -2.61 0.00
Rpl3-ps1 172.77 -1.90 0.00
Rps10-ps2 42.88 -2.09 0.00
Gm37035 211.52 -1.01 0.00
Rpl17-ps3 51.36 -3.14 0.00
Rpl31-ps8 53.05 -2.11 0.00
Rpl19-ps11 98.62 -2.73 0.00
Rps16-ps2 57.35 -3.14 0.00
Gm6863 46.80 -2.18 0.00
ENSMUSG00000141748 74.57 -1.59 0.00
ENSMUSG00000121655 13.61 -2.66 0.00
ENSMUSG00000139771 129.19 -3.08 0.00
Gm13456 180.96 -2.20 0.00
Eno1b 44.27 -3.16 0.00
Gm12251 12.81 -3.41 0.00
ENSMUSG00000138427 12.28 -3.59 0.00
Pgam1-ps2 72.13 -2.81 0.00
Eif4a-ps4 71.83 -1.69 0.00
ENSMUSG00000137056 11.14 -3.02 0.00
Gm8399 28.07 -2.54 0.00
Gm5537 109.46 -2.16 0.00
Uba52rt 148.31 -2.24 0.00
Rps25-ps1 12.01 -4.61 0.00
Gm7666 20.71 -3.19 0.00
Gm14703 175.77 -2.81 0.00
Gm13611 10.47 -5.35 0.00
Gm45855 12.51 -4.57 0.00
ENSMUSG00000121783 428.90 -1.68 0.00
Gm6136 55.33 -1.83 0.00
Gm14494 11.31 -2.92 0.00
Rps24-ps3 28.76 -3.44 0.00
ENSMUSG00000123149 27.56 -2.49 0.00
Gm10053 130.76 -2.69 0.00
Gm9625 19.65 -1.92 0.00
4930527F14Rik 39.80 -1.21 0.00
Gm14121 10.39 -2.82 0.00
Gm6560 71.75 -2.16 0.00
Gm14150 18.23 -2.84 0.00
Glns-ps1 25.56 -2.45 0.00
Gm5499 26.45 -2.14 0.00
Gm9794 52.55 -2.52 0.00
Gm4202 63.44 -1.78 0.00
Gstp-ps 13.24 -3.34 0.00
Actr3-ps 17.22 -2.37 0.00
ENSMUSG00000121784 136.68 -1.95 0.00
ENSMUSG00000128633 86.75 -4.38 0.00
Gm12183 37.50 -1.96 0.00
Gm4366 83.48 -2.26 0.00
Gm10039 17.54 -2.61 0.00
Kansl2-ps 10.47 -2.96 0.00
ENSMUSG00000121777 294.50 -1.65 0.00
1810049J17Rik 12.04 -3.94 0.00
Rpl36-ps12 24.73 -2.47 0.00
Gm6344 8.81 -4.16 0.00
Rplp2-ps1 21.23 -4.61 0.00
Rps27rt 122.01 -2.79 0.00
Rpl18-ps2 19.29 -3.18 0.00
Eef2-ps2 17.43 -2.56 0.00
Gstm2-ps1 8.92 -4.10 0.00
Ap2m1-ps 148.46 -1.21 0.00
A730035I17Rik 34.80 -1.66 0.00
Gm12892 85.93 -2.14 0.00
ENSMUSG00000142490 15.19 3.15 0.00
Adrm1b 21.18 -2.49 0.00
Tmsb10b 24.13 -1.53 0.00
Pcsk1n 9172.98 -1.04 0.00
Atp6v0c-ps2 39.99 -1.85 0.00
Gm5422 13.37 -3.08 0.00
Rps23-ps1 43.83 -2.53 0.00
mt-Co2 48324.30 -1.24 0.00
Gm2999 17.14 -2.94 0.00
Gm12669 23.56 -1.70 0.00
Pomc 219.02 -3.31 0.00
Vcp-rs 48.11 -1.54 0.00
Gm5844 25.03 -1.69 0.00
Mif-ps4 9.36 -4.22 0.00
Gm16439 7.56 -3.26 0.00
Fam221b 55.45 -1.14 0.00
ENSMUSG00000132147 11.74 -3.28 0.00
Ube2n-ps1 15.00 -2.67 0.00
Gm12346 127.56 -1.54 0.00
Nudc-ps1 12.10 -2.31 0.00
Gm56672 23.34 -3.54 0.00
Gm16437 12.88 -2.43 0.00
Gm7658 10.53 -3.15 0.00
Gm20431 112.10 -6.85 0.00
Gm2614 8.89 -4.58 0.00
Rps13-ps2 20.99 -2.55 0.00
Gm6204 30.40 -4.01 0.00
Tmem238 64.57 -1.07 0.00
Mxd4os1 28.54 -1.09 0.00
Gm2225 11.77 -3.48 0.00
Gm10250 43.79 -2.51 0.00
Arhgap27os2 11.76 -2.11 0.00
Oxt 153.32 -1.72 0.00
Sms-ps 16.46 -2.00 0.00
Gm16105 88.53 1.26 0.00
Rpl6l 18.78 -2.20 0.00
Gm7536 90.29 -2.38 0.00
ENSMUSG00000132287 18.32 -2.60 0.00
Nicol1 350.21 -1.10 0.00
Gm9493 36.54 -2.81 0.00
Rps18-ps6 38.82 -3.38 0.00
Hspe1-rs1 14.13 -2.73 0.00
Rpl7-ps7 6.39 -3.32 0.00
Ahcyl 14.28 -2.46 0.00
Gm28901 62.18 -1.00 0.00
Gchfr 23.93 -1.65 0.00
Gm3724 13.47 -1.97 0.00
Gm4459 11.14 -2.75 0.00
Pam16l 10.51 -2.69 0.00
Gm10221 23.48 -3.15 0.00
Rps26-ps1 13.86 -6.95 0.00
Gm12174 19.91 -2.62 0.00
Rps15-ps2 9.49 -3.20 0.00
ENSMUSG00000126561 34.97 -1.61 0.00
Tpm3-rs7 18.15 -1.87 0.00
Pabpc1l2b 14.98 -7.06 0.00
Cftr 21.39 1.15 0.00
Oaz1-ps 65.74 -2.28 0.00
ENSMUSG00000131289 12.58 -2.17 0.00
Gm11964 4.98 -4.25 0.00
Rpl9-ps4 20.03 -3.87 0.00
Psma5-ps 12.67 -2.59 0.00
Tpi-rs11 10.56 -3.56 0.00
Btf3-ps1 16.57 -2.40 0.00
Gm5421 16.88 -2.26 0.00
Nutf2-ps1 30.96 -1.46 0.00
Gm6055 11.02 -3.01 0.00
ENSMUSG00000125136 21.82 -1.29 0.00
Gm7730 3.19 -4.81 0.00
2510046G10Rik 15.90 -1.43 0.00
Gm15421 13.67 -2.49 0.00
Eef1a1-ps1 24.90 -1.35 0.00
ENSMUSG00000127515 11.16 -2.01 0.00
Gm5560 10.04 -2.85 0.00
Gm15519 5.33 -3.76 0.00
Gm5835 24.58 -1.90 0.00
Rps7-ps3 48.23 -2.63 0.01
ENSMUSG00000138717 15.30 -2.50 0.01
Gm15501 26.74 -3.59 0.01
Gm3571 7.39 -3.84 0.01
AK157302 15.86 -2.08 0.01
Gm3226 15.54 -1.82 0.01
Gm56991 52.52 -1.47 0.01
Erhrt-ps 11.30 -2.67 0.01
Glo1-ps 6.39 -2.98 0.01
Gm45051 15.47 -1.51 0.01
Rab11b-ps2 13.92 -2.65 0.01
APOE 28177.85 2.11 0.01
4632415L05Rik 9.66 -6.42 0.01
Gm10263 13.44 -4.37 0.01
ENSMUSG00000143530 6.95 -2.45 0.01
ENSMUSG00000132604 23.23 -3.44 0.01
Gm37123 5.34 2.17 0.01
Gm13461 15.23 -2.25 0.01
Lbhd2 34.68 -1.14 0.01
Scand1 356.19 -1.03 0.01
Mrpl23-ps1 14.71 -2.43 0.01
1600020E01Rik 189.20 -1.24 0.01
Gm10642 37.78 -1.46 0.01
Gpi-ps 55.85 -2.14 0.01
ENSMUSG00000123407 5.08 -3.70 0.01
Gm17167 34.44 3.78 0.01
Gm21399 5.26 -2.42 0.01
Gm57848 39.85 1.26 0.01
Gm13835 39.37 -1.54 0.01
Gm10819 14.98 -2.31 0.01
Ldhb-ps 44.40 -2.07 0.01
Gm5905 14.34 -2.74 0.01
H3c15 37.44 -1.05 0.01
ENSMUSG00000122915 11.81 -2.76 0.01
Gm12966 16.76 -1.65 0.01
Gm21986 58.58 -2.33 0.01
Gm5424 11.62 -2.10 0.01
ENSMUSG00000125669 11.25 -2.30 0.01

6.1.2.3 Females only

There are 265 significantly differentially expressed genes (FDR < 0.01, |log2FC| > 1) in the brain between female Cre-AAV and GFP control switch mice.

Diagnostic plots for the DE analysis

  • A histogram enriched for low p-values shows the presence of true differential expression (deviation from the uniform null), rather than an all-noise result.
  • The log(baseMean) distribution for significant genes being skewed toward moderate–high counts indicates findings are driven by well-expressed features, not low-count noise that can inflate fold-changes and p-values.
Significantly differentially expressed genes in brain
Cre-AAV and GFP control
(FDR < 0.01, |log2FC| > 1)
gene baseMean log2FoldChange padj
Rn7s1 578.80 2.53 0.00
Gm22009 141.75 4.76 0.00
Rn18s-rs5 236649.28 1.63 0.00
Rn7sk 507.70 2.20 0.00
Lars2 30132.78 1.27 0.00
Rpl35a-ps2 45.69 -23.76 0.00
Gm56350 30.27 -23.13 0.00
Gm49388 25.31 -22.96 0.00
Cdr1 107.69 1.82 0.00
Gm15427 57.30 -3.29 0.00
Rpl19-ps11 101.22 -2.82 0.00
Gm11478 46.34 -3.62 0.00
Oaz1-ps 60.14 -2.85 0.00
Rpl17-ps3 51.82 -3.01 0.00
Gm7536 100.26 -2.78 0.00
Rps16-ps2 55.74 -3.60 0.00
Rps7-ps3 50.66 -3.34 0.00
ENSMUSG00000140457 498.54 1.06 0.00
Uba52rt 142.29 -2.30 0.00
Gm4149 37.20 -3.40 0.00
Eno1b 50.07 -3.10 0.00
Gm10073 41.72 -3.90 0.00
Gm5526 11.65 -7.03 0.00
Gpi-ps 60.12 -2.71 0.00
Rps23-ps1 53.22 -3.02 0.00
Rpl3-ps1 183.86 -1.94 0.00
Gm4366 76.23 -2.33 0.00
B020010K11Rik 35.08 -3.08 0.00
Rpsa-ps10 71.75 -2.89 0.00
Gm12892 87.07 -2.61 0.00
Tpt1-ps3 60.04 -2.57 0.00
Rps19-ps6 37.77 -3.76 0.00
Cox5b-ps 35.77 -2.97 0.00
Rpl34-ps1 28.65 -4.33 0.00
Rps18-ps5 22.58 -5.55 0.00
Rpl18-ps2 18.60 -5.55 0.00
ENSMUSG00000121784 148.22 -2.03 0.00
Gm9493 25.84 -3.09 0.00
Rpl35rt 137.02 -3.73 0.00
Gm9385 44.07 -2.78 0.00
Rpl17-ps10 72.91 -2.68 0.00
Gm8226 76.06 -1.91 0.00
ENSMUSG00000128633 88.74 -3.90 0.00
Gm4202 66.20 -1.74 0.00
Rps18-ps6 35.64 -3.35 0.00
Rps6-ps4 116.79 -1.96 0.00
Rps24-ps3 25.65 -3.03 0.00
ENSMUSG00000132604 23.11 -3.60 0.00
ENSMUSG00000143433 24.05 -4.55 0.00
Gm16437 14.40 -3.97 0.00
Gm12481 45.88 -7.82 0.00
Gm6560 70.09 -2.32 0.00
Gm4332 26.52 -3.81 0.00
1810049J17Rik 15.50 -4.71 0.00
mt-Co2 58270.43 -1.22 0.00
Rpl14-ps1 55.66 -2.75 0.00
Gm15772 30.85 -3.25 0.00
Malat1 18026.65 1.98 0.00
Ldhb-ps 45.47 -2.21 0.00
Rps3a2 69.23 -2.80 0.00
Rps13-ps1 28.55 -3.68 0.00
Pcsk1n 9963.48 -1.11 0.00
Gm14586 30.02 -3.35 0.00
Gm12174 16.50 -3.85 0.00
Gm9794 54.91 -2.29 0.00
Pgam1-ps2 64.52 -2.52 0.00
Rpl28-ps1 36.76 -2.66 0.00
Nicol1 368.74 -1.22 0.00
Nme3 454.49 -1.08 0.00
Gm4459 10.91 -3.78 0.00
Gm5499 27.49 -2.64 0.00
Fbxl15 319.39 -1.05 0.00
ENSMUSG00000121779 75.07 -1.60 0.00
Gm10053 144.97 -2.71 0.00
H2aj 808.32 -1.05 0.00
ENSMUSG00000128869 20.02 -3.77 0.00
Rps25-ps1 14.79 -4.19 0.00
Rpl31-ps8 55.61 -2.02 0.00
Scand1 383.28 -1.20 0.00
Gm10250 38.72 -2.38 0.00
Rps10-ps2 41.75 -2.20 0.00
ENSMUSG00000137224 93.43 -1.85 0.00
Gm2225 15.75 -3.89 0.00
Gm10221 18.99 -3.22 0.00
Atp6v0c-ps2 37.49 -2.07 0.00
Gm6204 26.63 -3.69 0.00
Gm8730 21.54 -4.27 0.00
Btf3l4b 22.29 -1.95 0.00
Gm10288 103.00 -3.13 0.00
Nr2f6 642.28 -1.00 0.00
Ap2m1-ps 153.71 -1.40 0.00
Nudc-ps1 12.83 -3.19 0.00
Rpl9-ps6 208.43 -2.43 0.00
Gm37811 58.51 -1.77 0.00
ENSMUSG00000135935 65.49 6.02 0.00
Gm13436 26.37 -3.63 0.00
Vcp-rs 48.71 -1.96 0.00
Rpl6l 21.80 -2.32 0.00
Glns-ps1 29.13 -3.00 0.00
Eef2-ps2 16.08 -3.65 0.00
ENSMUSG00000121793 90.21 -3.07 0.00
Rps27rt 133.38 -2.82 0.00
Gm6789 38.76 -2.16 0.00
ENSMUSG00000138136 23.55 -2.07 0.00
ENSMUSG00000139771 156.48 -3.15 0.00
9530059O14Rik 33.09 1.86 0.00
Fam221b 61.82 -1.33 0.00
Gm8566 19.16 -2.80 0.00
Gm13456 190.04 -2.47 0.00
Gm13835 46.99 -1.89 0.00
Gm44442 149.19 -1.81 0.00
ENSMUSG00000126438 9.67 -4.74 0.00
H3c15 43.23 -1.43 0.00
Gm37035 236.47 -1.27 0.00
ENSMUSG00000131289 11.99 -2.86 0.00
Gm2223 21.79 -2.19 0.00
Gm5805 11.79 -4.29 0.00
Gm13611 9.21 -6.08 0.00
Gm5436 13.44 -3.74 0.00
Gm10263 11.86 -4.65 0.00
Gm11223 36.70 -2.13 0.00
Gm37899 20.43 2.35 0.00
Gm7600 17.47 -4.26 0.00
Hspe1-rs1 14.06 -3.89 0.00
Endog 314.93 -1.05 0.00
ENSMUSG00000138427 16.21 -3.65 0.00
Gm49325 122.37 1.01 0.00
Gm12346 130.36 -1.12 0.00
ENSMUSG00000121777 292.85 -1.95 0.00
Rps27a-ps2 47.55 -2.18 0.00
Gm6863 45.00 -2.05 0.00
Gm21986 68.28 -1.64 0.00
Gm13680 10.46 -2.97 0.00
Actr3-ps 18.75 -2.38 0.00
4933431K14Rik 76.28 -1.06 0.00
Gm12350 18.05 -3.16 0.00
Gm7308 38.06 -2.11 0.00
Rn7s2 77.59 9.68 0.00
Tmem238 66.11 -1.10 0.00
Hadhb-ps 30.08 -1.50 0.00
Rps15a-ps7 16.15 -3.10 0.00
Rps10-ps1 14.11 -3.94 0.00
Gm13461 14.94 -2.68 0.00
Gm45855 13.17 -3.60 0.00
Kcnq1ot1 382.85 1.02 0.00
Rpl37rt 34.71 -8.60 0.00
Eif4a-ps4 80.28 -1.36 0.00
Gm3571 8.06 -4.83 0.00
Gm10052 39.44 -1.60 0.00
Rpl10a-ps1 67.61 -1.53 0.00
Rpl9-ps4 24.26 -2.76 0.00
ENSMUSG00000121655 12.87 -2.72 0.00
Erhrt-ps 13.16 -3.67 0.00
Gm5424 13.49 -2.69 0.00
Rps15-ps2 9.91 -3.50 0.00
Mif-ps4 12.67 -4.79 0.00
Gm8355 55.12 -1.52 0.00
Gm8203 16.03 -2.70 0.00
Gm10036 11.59 -3.51 0.00
Gm9816 26.01 -2.34 0.00
Gm5835 21.97 -2.14 0.00
Gm2614 7.74 -3.94 0.00
Gm13066 16.48 -3.17 0.00
mt-Ts1 6.47 -5.57 0.00
4632415L05Rik 19.89 -7.80 0.00
Gm5421 15.84 -2.24 0.00
Yjefn3 131.82 -1.21 0.00
Gm8399 33.76 -2.03 0.00
Rab11b-ps2 12.32 -2.56 0.00
Gm9625 25.86 -1.92 0.00
Gstp-ps 13.73 -3.23 0.00
Gm42583 29.71 2.14 0.00
Gm7816 22.67 -2.32 0.00
Nrtn 73.39 -1.73 0.00
Gm7666 19.23 -2.84 0.00
Gm6136 48.86 -1.53 0.00
ENSMUSG00000123407 4.74 -5.12 0.00
Gm12254 18.46 -2.09 0.00
ENSMUSG00000123314 87.48 -1.24 0.00
Rpl36a-ps2 18.97 -2.25 0.00
Gm14150 18.33 -2.82 0.00
Aldoart1 15.76 -2.96 0.00
Mrpl23-ps1 14.71 -3.54 0.00
Cdk2ap1rt 43.71 -1.83 0.00
Crlf2 282.80 -1.02 0.00
Gm11175 17.39 -1.75 0.00
Gm2999 18.90 -2.59 0.00
Rpl23a-ps3 33.27 -2.58 0.00
Rpph1 25.44 1.96 0.00
Rps26-ps1 14.33 -7.33 0.00
Gal 89.53 -1.06 0.00
Ube2srt 24.01 -2.52 0.00
Gm10819 16.58 -2.68 0.00
Gm9531 12.27 -2.56 0.00
Rpl7-ps7 6.87 -3.17 0.00
Gm37530 13.26 2.12 0.00
ENSMUSG00000138717 20.46 -1.93 0.00
Gadd45g 397.60 -1.05 0.00
Gm5905 18.63 -2.68 0.00
Gm6180 23.98 -2.06 0.00
Sap18b 31.02 -2.11 0.00
Gm9824 28.37 -1.77 0.00
ENSMUSG00000132287 13.72 -3.34 0.00
Gm12183 40.77 -1.95 0.00
Kcng3 28.31 1.19 0.00
Btf3-ps1 13.70 -2.15 0.00
ENSMUSG00000139219 17.51 1.76 0.00
Gm10163 49.84 -1.60 0.00
Cox7a1 40.34 -1.02 0.00
Gm6170 7.76 -4.30 0.00
ENSMUSG00000140944 15.50 -2.30 0.00
Zfp781a 61.15 1.05 0.00
ENSMUSG00000121783 451.50 -1.43 0.00
Gm14121 12.44 -2.59 0.00
Gm6344 10.55 -3.14 0.00
Gm56991 65.25 -1.27 0.00
Hmgn2-ps 138.07 -1.05 0.00
Mrip-ps 13.92 -2.09 0.00
Gm12251 10.37 -2.88 0.00
Gm12966 17.33 -1.95 0.00
Gm2423 24.69 -2.28 0.00
Gm9755 9.72 -2.78 0.00
Gm5844 27.67 -1.54 0.00
Tmsb10b 26.00 -1.76 0.00
G630016G05Rik 112.76 1.10 0.00
Eif3j2 21.21 -2.10 0.00
ENSMUSG00000121782 4.70 -4.45 0.01
Gm16439 9.53 -2.92 0.01
Gm37310 20.42 1.46 0.01
D830035M03Rik 19.33 -1.43 0.01
Gm11964 6.48 -3.88 0.01
1700034P13Rik 49.33 1.67 0.01
Gm5456 4.30 -4.97 0.01
Nutf2-ps1 35.09 -1.50 0.01
Gstm2-ps1 10.97 -3.16 0.01
Gm15519 6.53 -3.13 0.01
Gm12918 86.65 -2.99 0.01
H2ac19 228.40 -1.62 0.01
Adrm1b 15.11 -1.84 0.01
Pglyrp1 178.11 -1.02 0.01
Col6a5 12.20 2.09 0.01
Gm44170 36.56 -2.14 0.01
Tpm3-rs7 20.05 -1.76 0.01
Gm14494 14.32 -1.97 0.01
5730405O15Rik 22.94 1.25 0.01
Hspd1-ps3 18.08 -1.91 0.01
Rpl36-ps12 24.74 -2.19 0.01
Avp 269.53 -1.45 0.01
Scp2-ps2 5.67 -3.77 0.01
Gm10039 13.74 -2.24 0.01
ENSMUSG00000140290 28.88 -1.33 0.01
Tpi-rs11 11.26 -3.46 0.01
Impdh2-ps 9.35 -2.45 0.01
ENSMUSG00000136525 53107.71 1.97 0.01
Gm57504 53.53 -1.11 0.01
Gm43843 48.27 1.44 0.01
Ube2n-ps1 16.58 -2.23 0.01
Prkcz2 28.06 -1.73 0.01
Ccdc171 34.14 1.04 0.01
4921516A02Rik 14.38 -2.85 0.01
ENSMUSG00000129048 35.44 1.78 0.01
ENSMUSG00000133032 12.16 2.10 0.01
Ahcyl 13.11 -2.55 0.01
ENSMUSG00000129696 20.90 1.14 0.01
Gm56769 28.84 -1.66 0.01

6.1.2.4 Common DEGs in males and females

Differential expression analysis comparing Cre-AAV and GFP control groups in brain identified a large number of significantly altered transcripts (FDR < 0.01, |log₂FC| > 1). To focus on robust and biologically relevant signals, we intersected DEGs detected in both male and female mice.

There were 178 common DEGs shared in male and females. The majority corresponded to ribosomal and uncharacterized pseudogenes, reflecting global transcriptional perturbations rather than specific pathway activation.

gene
Gm16437
Fbxl15
Tmem238
Pcsk1n
Nrtn
Adrm1b
Gm5436
Gpi-ps
Gm6863
Fam221b
Oaz1-ps
Gm8399
Gm9493
Ldhb-ps
Scand1
Gm11223
Gm5424
Rpl14-ps1
Rpsa-ps10
Gm8566
Ahcyl
4632415L05Rik
Rps27rt
Gm6180
Rpl18-ps2
Gm7536
Tpm3-rs7
Rpl28-ps1
Rps27a-ps2
Gm10052
Gm10053
Eno1b
Aldoart1
Rps26-ps1
Gm10073
Rps16-ps2
Sap18b
Gm15772
Rpl9-ps6
Rps3a2
Erhrt-ps
Hadhb-ps
Gm8730
H2ac19
mt-Co2
Gm13611
Gm12918
Rps13-ps1
Gm10263
Gm10163
Rps25-ps1
Gm7666
Gm10221
Rpl31-ps8
Uba52rt
Rpl34-ps1
Gm10250
Rps18-ps6
Gm10288
Gm12966
Nicol1
Gm5499
Rps15-ps2
Nutf2-ps1
Gm16439
Nme3
Gm4149
Gm10819
Mrpl23-ps1
Rpl23a-ps3
Rpl35rt
Cox5b-ps
Atp6v0c-ps2
Gm12174
Gm9385
Gm11964
Rps24-ps3
Gm15427
H3c15
Rps15a-ps7
Rpl19-ps11
Gm7308
Ap2m1-ps
Rps6-ps4
Rpl17-ps10
Gm13461
Pgam1-ps2
Glns-ps1
Actr3-ps
Gm12183
Gm13456
Eef2-ps2
Gm14150
Gm5844
Gm14494
Gm14121
Vcp-rs
Gm15519
Gm14586
Gm4459
Mif-ps4
Gm12892
Gm13436
Gm12346
Gm11478
Gm6136
Rpl3-ps1
Gm12251
Rpl10a-ps1
Gm12254
Gm9816
Gm13835
Btf3-ps1
Gm3571
Rpl6l
Gm4202
Gm10039
Rpl36-ps12
Tmsb10b
Gm8355
Gm6344
Rpl9-ps4
Rps7-ps3
Rab11b-ps2
Gm21986
Rps19-ps6
1810049J17Rik
Gm5421
Gm9625
Rps10-ps2
Gm8226
Rps23-ps1
Eif4a-ps4
Gm5835
Gm8203
Gm37035
Gm56350
Gstp-ps
Gm6560
Rpl36a-ps2
Gm6204
Gm4332
Tpi-rs11
Ube2n-ps1
Rpl7-ps7
Gm9794
Gstm2-ps1
Gm4366
Prkcz2
Gm7600
Gm2225
Gm5905
Nudc-ps1
Gm45855
Rps18-ps5
Gm2614
Rpl17-ps3
Gm2999
Hspe1-rs1
Gm6789
Ube2srt
Gm56991
ENSMUSG00000121655
ENSMUSG00000121777
ENSMUSG00000121779
ENSMUSG00000121783
ENSMUSG00000121784
ENSMUSG00000121793
ENSMUSG00000123407
ENSMUSG00000128633
ENSMUSG00000131289
ENSMUSG00000132287
ENSMUSG00000132604
ENSMUSG00000137224
ENSMUSG00000138427
ENSMUSG00000138717
ENSMUSG00000139771
ENSMUSG00000143433

Filtering out pseudogenes, unannotated loci (Gm*), mitochondrial genes, and Ensembl-only identifiers yielded 25 high-confidence nuclear genes consistently dysregulated across sexes, representing the shared brain response to Cre-mediated ApoE4→ApoE2 conversion.

Fbxl15, Tmem238, Pcsk1n, Nrtn, Adrm1b, Fam221b, Scand1, Ahcyl, 4632415L05Rik, Tpm3-rs7, Eno1b, Aldoart1, Sap18b, H2ac19, Uba52rt, Nicol1, Nme3, H3c15, Vcp-rs, Tmsb10b, 1810049J17Rik, Tpi-rs11, Prkcz2, Hspe1-rs1, Ube2srt

The set included genes involved in proteostasis and ubiquitin signaling (Adrm1b, Uba52rt, Ube2srt, Vcp-rs, Hspe1-rs1), cytoskeletal organization (Tpm3-rs7, Tmsb10b), and energy metabolism (Eno1b, Aldoart1, Tpi-rs11). Additional changes were observed in genes implicated in neuronal signaling and synaptic modulation, including Nrtn (neurturin), Pcsk1n, Ahcyl, and Prkcz2.

Several of these transcripts (Adrm1b, Eno1b, Sap18b, Vcp-rs, Hspe1-rs1) overlapped with those altered in the liver, indicating a shared transcriptional response to ApoE2 expression.